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Fibroblast Collapse and Therapeutic Implications

Gary J. Fisher, PhD; James Varani, PhD; John J. Voorhees, MD

Arch Dermatol. 2008;144(5):666-672.

Skin appearance is a primary indicator of age. During the last decade, substantial progress has been made toward understanding underlying mechanisms of human skin aging. This understanding provides the basis for current use and new development of antiaging treatments. Our objective is to review present state-of-the-art knowledge pertaining to mechanisms involved in skin aging, with specific focus on the dermal collagen matrix. A major feature of aged skin is fragmentation of the dermal collagen matrix. Fragmentation results from actions of specific enzymes (matrix metalloproteinases) and impairs the structural integrity of the dermis. Fibroblasts that produce and organize the collagen matrix cannot attach to fragmented collagen. Loss of attachment prevents fibroblasts from receiving mechanical information from their support, and they collapse. Stretch is critical for normal balanced production of collagen and collagen-degrading enzymes. In aged skin, collapsed fibroblasts produce low levels of collagen and high levels of collagen-degrading enzymes. This imbalance advances the aging process in a self-perpetuating, never-ending deleterious cycle. Clinically proven antiaging treatments such as topical retinoic acid, carbon dioxide laser resurfacing, and intradermal injection of cross-linked hyaluronic acid stimulate production of new, undamaged collagen. Attachment of fibroblasts to this new collagen allows stretch, which in turn balances collagen production and degradation and thereby slows the aging process. Collagen fragmentation is responsible for loss of structural integrity and impairment of fibroblast function in aged human skin. Treatments that stimulate production of new, nonfragmented collagen should provide substantial improvement to the appearance and health of aged skin.

Author Affiliations: Departments of Dermatology (Drs Fisher and Voorhees) and Pathology (Dr Varani), Medical School, University of Michigan, Ann Arbor.